This invention relates to novel prostanoic acid derivatives, processes for the preparation and use thereof, and to novel intermediates produced in these processes.
Prostaglandins are C-20-unsaturated fatty acids showing a variety of physiological effects (T. O. Oesterling et al., J. Pharmaceutical Sciences 61 [1972] 1861-1895). Such effects are, for example, vasodilation, bronchodilatation, inhibition of the stomach acid secretion, suppression of the aggregation of blood platelets. Various natural prostaglandins, such as, for example, prostaglandin E.sub.2 and prostaglandin F.sub.2.alpha., are suitable for triggering menstruation, for including abortions and for the induction of labor.
The conventional prostaglandins are derivatives of prostanoic acid having the following formula: ##STR4##
Examples of known prostaglandins, called PG hereinbelow, are: ##STR5##
PG E.sub.2, PG F.sub.2.alpha., PG A.sub.2, PG D.sub.2 are in conformance with the compounds of the PG'.sub.1 series with respect to their basic structure but linking of the C-5 and C-6 atoms is different. In the PG'.sub.2 series, the C-5 and C-6 carbon atoms are linked by a cis-double bond. PG F.sub.2.alpha. has the formula: ##STR6##
PG E.sub.3, PG F.sub.3.alpha., and PG A.sub.3 differ from the corresponding PG'.sub.2 compounds in that the C-17 and C-18 atoms are linked by a cis-double bond.
PG F.sub.3.alpha. has the formula: ##STR7##
It is generally known that the physiological effects of the prostaglandins are only of short duration in the mammalian organism as well as in vitro, since they are rapidly converted into pharmacologically inactive metabolic products. Thus, a physiologically inactive metabolite is formed by oxidation of the allylic hydroxy function on the C-15 atom due to 15-hydroxyprostaglandin dehydrogenases. From PG F.sub.2.alpha., for example, the following 13,14-dihydro-15-dehydro derivative is formed by this oxidation as well as by a hydrogenation step, as the main metabolite (E. Granstroem and B. Samuelson, Eur. J. Biochem. 10 [1969] 411): ##STR8## which possesses the physiological effects typical for this class of compounds only to a very greatly diminished extent.
Therefore, it has been desired to develop prostaglandin analogs having an activity spectrum comparable to that of the natural prostaglandins and to make structural changes by means of which the duration and selectivity of effectiveness are increased.
In U.S. Application Ser. No. 472,738, filed May 23, 1974, ketals of natural 15-dehydroprostaglandins are described. It has now been found that, by modifying the lower prostaglandin side chain while retaining the ketal structure element, substantially increased physiological effects are being evoked.
The novel ketals surpass in their activity the natural prostaglandins. Furthermore, the effectiveness lasts over a longer period of time. The 15-ketoprostaglandins corresponding to these ketals show the physiological effects typical for prostaglandins only in greatly weakened form. Therefore, the advantageous properties of the novel compounds could not be expected. The novel compounds moreover have the advantage that they are very readily accessible, do not have a center of asymmetry on the C-15 atom, and thus can be obtained in the pure form without any great technical expenditure.